The 5-HT1A receptor agonist buspirone improves esophageal motor function and symptoms in systemic sclerosis: a 4-week, open-label trial

George P Karamanolis, Stylianos Panopoulos, Konstantinos Denaxas, Anastasios Karlaftis, Alexandra Zorbala, Dimitrios Kamberoglou, Spiros D Ladas, Petros P Sfikakis, George P Karamanolis, Stylianos Panopoulos, Konstantinos Denaxas, Anastasios Karlaftis, Alexandra Zorbala, Dimitrios Kamberoglou, Spiros D Ladas, Petros P Sfikakis

Abstract

Background: Acute administration of the oral 5-HT1A receptor agonist buspirone, which is commonly used as an anxiolytic drug, may improve compromised lower esophageal sphincter function. In an open-label trial we assessed the effects of buspirone on esophageal motor function and symptoms in patients with esophageal involvement associated with systemic sclerosis (SSc).

Methods: Thirty consecutive patients with SSc and symptomatic esophageal involvement, despite treatment with proton pump inhibitors, underwent high resolution manometry and chest computed tomography for assessment of motor function and esophageal dilatation, respectively. Regurgitation, heartburn, dysphagia, and chest pain severity was subjectively scored by visual analog scales. Manometric parameters (primary endpoint) and symptom severity (secondary endpoint) were re-examined after 4-week daily administration of 20 mg buspirone. Other medications remained unchanged.

Results: Eight patients did not complete the trial because of buspirone-associated dizziness (n = 2), or nausea (n = 2), or reluctancy to undergo final manometry. In the remaining 22 patients lower esophageal sphincter (LES) resting pressure increased from 7.7 ± 3.9 to 12.2 ± 4.6 mmHg (p = 0.00002) after buspirone administration; other manometric parameters did not change. Statistical analysis revealed negative correlation between individual increases in resting LES pressure and supra-aortic esophageal diameter (r = -0.589, p = 0.017), suggesting a more beneficial effect in patients with less severely affected esophageal function. Heartburn and regurgitation scores decreased at 4 weeks compared to baseline (p = 0.001, and p = 0.022, respectively).

Conclusion: Our findings warrant more conclusive evaluation with a double-blind controlled study; however, buspirone could potentially be given under observation for objective improvement in all patients with SSc who report reflux symptoms despite undergoing standard treatment.

Trial registration: ClinicalTrials.gov Identifier: NCT02363478 Registered: 21-02-2014.

Keywords: Buspirone; Esophageal motility; Reflux symptoms; Scleroderma.

Figures

Fig. 1
Fig. 1
Change in lower esophageal sphincter (LES) pressure in each individual at baseline and after 4-week daily oral administration of 20 mg buspirone

References

    1. Varga J, Abraham D. Systemic sclerosis: a prototypic multisystem fibrotic disorder. J Clin Invest. 2007;117:557–67. doi: 10.1172/JCI31139.
    1. Clements PJ, Becvar R, Drosos AA, Ghattas L, Gabrielli A. Assessment of gastrointestinal involvement. Clin Exp Rheumatol. 2003;21(Suppl 29):S15–8.
    1. Ebert EC. Esophageal disease in scleroderma. J Clin Gastroenterol. 2006;40:769–75. doi: 10.1097/01.mcg.0000225549.19127.90.
    1. Ntoumazios SK, Voulgari PV, Potsis K, Koutis E, Tsifetaki N, Assimakopoulos DA. Esophageal involvement in scleroderma: gastroesophageal reflux, the common problem. Semin Arthritis Rheum. 2006;36:173–81. doi: 10.1016/j.semarthrit.2006.08.002.
    1. Sallam H, McNearney TA, Chen JD. Systematic review: pathophysiology and management of gastrointestinal dysmotility in systemic sclerosis (scleroderma) Aliment Pharmacol Ther. 2006;23:691–712. doi: 10.1111/j.1365-2036.2006.02804.x.
    1. Karamanolis G, Panopoulos S, Karlaftis A, Denaxas K, Kamberoglou D, Sfikakis PP, Ladas SD. Beneficial effect of the 5-HT1A receptor agonist buspirone on esophageal dysfunction associated with systemic sclerosis: a pilot study. United Eur Gastroenterol J. 2015;3:266–71. doi: 10.1177/2050640614560453.
    1. Hempfling C, Neuhuber WL, Worl J. Serotonin-immunoreactive neurons and mast cells in the mouse esophagus suggest involvement of serotonin in both motility control and neuroimmune interactions. Neurogastroenterol Motil. 2012;24:e67–78. doi: 10.1111/j.1365-2982.2011.01797.x.
    1. Blonski W, Vela MF, Freeman J, Sharma N, Castell DO. The effect of oral buspirone, pyridostigmine, and bethanechol on esophageal function evaluated with combined multichannel esophageal impedance-manometry in healthy volunteers. J Clin Gastroenterol. 2009;43:253–60. doi: 10.1097/MCG.0b013e318167b89d.
    1. Di Stefano M, Papathanasopoulos A, Blondeau K, Vos R, Boecxstaens V, Farré R, et al. Effect of buspirone, a 5-HT1A receptor agonist, on esophageal motility in healthy volunteers. Dis Esophagus. 2012;25:470–6. doi: 10.1111/j.1442-2050.2011.01275.x.
    1. van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, et al. 2013 classification criteria for systemic sclerosis: an American college of rheumatology/European league against rheumatism collaborative initiative. Ann Rheum Dis. 2013;72(11):1747–55. doi: 10.1136/annrheumdis-2013-204424.
    1. Geeraerts B, Vandenberghe J, Van Oudenhove L, Gregory LJ, Aziz Q, Dupont P, et al. Influence of experimentally induced anxiety on gastric sensorimotor function in humans. Gastroenterology. 2005;129:1437–44. doi: 10.1053/j.gastro.2005.08.020.
    1. de Bortoli N, Martinucci I, Savarino E, Bellini M, Bredenoord AJ, Franchi R, et al. Proton pump inhibitor responders who are not confirmed as GERD patients with impedance and pH monitoring: who are they? Neurogastroenterol Motil. 2014;26:28–35. doi: 10.1111/nmo.12221.
    1. Pitrez EH, Bredemeier M, Xavier RM, Capobianco KG, Restelli VG, Vieira MV, et al. Oesophageal dysmotility in systemic sclerosis: comparison of HRTC and scintigraphy. Br J Radiol. 2006;79:719–24. doi: 10.1259/bjr/17000205.
    1. Breedenoord AJ, Fox M, Kahrilas PJ, Pandolfino JE, Schwizer W, Smout AJ, International High Resolution Manometry Working Group Chicago classification criteria of esophageal motility disorders defined in high resolution esophageal pressure topography. Neurogastroenterol Motil. 2012;24(Suppl 1):57–65. doi: 10.1111/j.1365-2982.2011.01834.x.
    1. Gao F, Liao D, Drewes AM, Gregersen H. Modelling the elastin, collagen and smooth muscle contribution to the duodenal mechanical behaviour in patients with systemic sclerosis. Neurogastroenterol Motil. 2009;21:914–e68. doi: 10.1111/j.1365-2982.2009.01314.x.
    1. McNearney TA, Sallam HS, Hunnicutt SE, Doshi D, Wollaston DE, Mayes MD, Chen J. Gastric slow waves, gastrointestinal symptoms and peptides in systemic sclerosis patients. Neurogastroenterol Motil. 2009;21:1269–e120. doi: 10.1111/j.1365-2982.2009.01350.x.
    1. Loane C, Politis M. Buspirone: what is it all about? Brain Res. 2012;1461:111–8. doi: 10.1016/j.brainres.2012.04.032.
    1. Vonk MC, Van Die CEV, Snoeren MM, Bhansing KJ, van Riel PL, Fransen J, van den Hoogen FH. Oesophageal dilatation on high-resolution computed tomography scan of the lungs as a sign of scleroderma. Ann Rheum Dis. 2008;67:1317–21. doi: 10.1136/ard.2007.081612.
    1. Pandey AK, Wilcox P, Mayo JR, Moss R, Ellis J, Brown J, et al. Oesophageal dilatation on high-resolution CT chest in systemic sclerosis: What does it signify? J Med Imag Radiat Oncol. 2011;55:551–5. doi: 10.1111/j.1754-9485.2011.02317.x.
    1. Nguyen C, Ranque B, Baubet T, Bérezné A, Mestre-Stanislas C, Rannou F, et al. Clinical, functional and health-related quality of life correlates of clinically significant symptoms of anxiety and depression in patients with systemic sclerosis: a cross-sectional survey. PLoS One. 2014;9:e90484. doi: 10.1371/journal.pone.0090484.
    1. Malcarne VL, Fox RS, Mills SD, Gholizadeh S. Psychosocial aspects of systemic sclerosis. Curr Opin Rheumatol. 2013;25:707–13. doi: 10.1097/01.bor.0000434666.47397.c2.
    1. Khanna D, Hays RD, Maranian P, Seibold JR, Impens A, Mayes MD, et al. Reliability and validity of the University of California, Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument. Arthritis Rheum. 2009;61(9):1257–63. doi: 10.1002/art.24730.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi